23 intensivistendagen ABSTRACTS ORAL PRESENTATIONS, O01-O010 and hyperoxic subjects with no apparent effects of both treatments. Furthermore, hypoxia and hyperoxia did not influence neutrophilic oxidative burst. Conclusion: Exposure of 3.5 hours to mild hypoxia or hyperoxia does not lead to cytokine production, nor does it change the capacity of leukocytes to produce inflammatory cytokines upon ex vivo stimulation. The extent and duration of hypoxia and hyperoxia used in this study appears not to result in induction of HIF1α or increased reactive oxygen production, respectively. Figure 1. Respiratory and hemodynamic parameters during 3.5 hours of hypoxia and hyperoxia. The oxygen status adjustment period is marked in grey. P-values calculated using two-way ANOVA (interaction term) O02 Alkaline phosphatase attenuates the inflammatory response in human proximal tubule epithelial cells: the potential mechanism of action of the observed beneficial effects in septic patients with acute kidney injury E. Peters 1,2, S. Heemskerk 1,2, R. Masereeuw 2, P. Pickkers 1 1 Department of Intensive Care Medicine, Nijmegen Institute for Infection, Inflammation and Immunity, Radboudumc, Nijmegen, The Netherlands, 2 Department of Pharmacology and Toxicology, Nijmegen Centre for Molecular Life Sciences, Radboudumc, Nijmegen, The Netherlands Figure 2. Neutrophil count during and after 3.5 hours of hypoxia and hyperoxia. The oxygen status adjustment period is marked in grey. P-values calculated using two-way ANOVA (interaction term) Background: Sepsis carries a high morbidity and mortality, especially when complicated by acute kidney injury (AKI). Currently, no treatment is available for sepsis-induced AKI. Two phase-ii trials showed that kidney function improved in critically ill patients with sepsis-induced AKI after treatment with the enzyme alkaline phosphatase (AP). 1,2 The mechanism of this beneficial effect on the kidney is unknown, but might be related to the dephosphorylation, and thereby detoxification, of endotoxin (lipopolysaccharide, LPS). We investigated the anti-inflammatory properties of AP by using a human proximal tubular cell model. Methods: Conditionally immortalized human proximal tubular epithelial cells (ciptec) were incubated with LPS (10 µg/ml) or TNF-α (10 ng/ml) to induce an inflammatory response. Recombinant human AP (10 U/ml) was added 2 hours prior to the inflammatory insult and the cytokine production of TNF-α, IL-6, and IL-8 was studied after 24 hours by ELISA. Supernatant of peripheral blood mononuclear cells (PBMCs), prestimulated for 24 hours with or without LPS (1 ng/ml), was added to the ciptec to mimic endotoxin-induced renal inflammation. AP was added 2 hours prior to this insult and IL-6 and IL-8 were measured after 24 hours. Data are expressed as mean ± SEM (n=5 per group) and the effect of AP was analyzed by one-way ANOVA. Results: AP pretreatment significantly reduced the LPS induced cytokine response of TNF-α (reduction 40.4 ± 7.9%, p<0.05), IL-6 (reduction 47.5 ± 3.1%, p<0.0001) and IL-8 (reduction 39.6±2.4%, p<0.0001) in ciptec (figure 1). Similar effects of AP were observed in ciptec stimulated with TNF-α, as the inflammatory response of IL-6 en IL-8 was significantly reduced by AP (IL-6: 21.0 ± 4.2%, p<0.05; IL-8: 21.6 ± 4.6%, p<0.05; figure 2). Inactive AP, lacking enzyme activity so it cannot dephosphorylate molecules, had no effect on both LPS- and TNF-α-induced

24 22 intensivistendagen 2014 ABSTRACTS ORAL PRESENTATIONS, O01-O010 Figure 1. AP significantly reduced the LPS induced cytokine response Figure 2. AP significantly reduced the TNF-α induced cytokine response Figure 3. AP significantly reduced the cytokine response induced by the supernatant of LPS-stimulated PBMCs cytokine response (figure 1 and 2). The supernatant of PBMCs, pre-incubated with LPS, induced the production of IL-6 and IL-8 in the ciptec. Stimulating the ciptec directly with 1 µg/ml LPS had no effect, demonstrating that the inflammatory response is induced by mediators present in the PBMC supernatant. AP treatment could significantly reduce this response (IL-6: 39.2 ± 9.6% reduced, p<0.05; IL-8: 34.9 ± 6.0%, p<0.05; figure 3). Conclusion: The dephosphorylating property of AP is responsible for the reduction of the cytokine response induced by LPS and TNF-α, as inactive AP had no effect. TNF-α and the inflammatory mediators in the PBMC supernatant itself cannot be dephosphorylated by AP, strongly suggesting that AP targets other molecules as well. A possible target might be ATP which is released by these cells upon stress conditions and can be con-

26 24 intensivistendagen 2014 ABSTRACTS ORAL PRESENTATIONS, O01-O010 age- and gender-matched non-delirious postoperative cardiac surgery patients. Patients were evaluated for delirium by a geriatrician, psychiatrist or neurologist using the Diagnostic and Statistical Manual of mental disorders IV criteria. Blinks were automatically extracted from electro-oculograms and eye movements from electro-encephalography recordings using independent component analysis. The number and duration of eye movements and blinks were compared between patients with and without delirium, based on the classification of the delirium experts described above. Eye movements were assessed during eyes open and eyes closed condition. Results: There were no significant differences between patients with and without delirium in age (mean ± SD 76 ± 5.7 versus 74 ± 8.6; p=0.21), gender (n=14 (54%) males versus n=16 (57%) males; p=0.81), bypass time (median(interquartile range) 129 (95-158) versus 108 (77-168); p=0.07) and Euroscore (median(interquartile range) 7 (6-9) versus 7 (5-8); p=0.17). During eyes open registrations, delirious patients showed, compared to non-delirious patients, a significant decrease in the number of blinks per minute and number of vertical eye movements per minute, as well as an increase in the average duration of blinks (table 1). During eyes closed, the average duration of horizontal eye movements was significantly increased in delirious patients compared to patients without delirium (table 1). Conclusion: This is the first study with automatic eye movement detection in delirious patients. We found that spontaneous eye movements, in particular blinks, were affected in delirious patients, which holds promise for the development of an objective tool to detect delirium. References 1. van Eijk MM, van den Boogaard M, van Marum RJ, et al: Routine use of the confusion assessment method for the intensive care unit: A multicenter study. Am J Respir Crit Care Med. 2011;184: Osse RJ, Tulen JHM, Hengeveld MW, et al: Screening methods for delirium: early diagnosis by means of objective quantification of motor activity patterns using wrist-actigraphy. Interact Cardiovasc Thorac Surg. 2009;8: O03 Delirium detection using EEG: what and how to measure? A.W. van der Kooi 1, I.J. Zaal 1, F.A.M. Klijn 2, H.L. Koek 3, T. Numan 1, R.C.A. Meijer 4, F.S.S. Leijten 5, A.J.C. Slooter 1 1 Department of Intensive Care Medicine, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands, 2 Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands, 3 Department of Geriatrics, University Medical Centre Utrecht, Utrecht, The Netherlands, 4 Department of Cardiothoracic Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands, 5 Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands Background: Despite its frequency and impact, delirium is poorly recognized with current screening methods in critically ill patients. 1 Electroencephalography (EEG) is a sensitive tool for delirium diagnosis, but inconvenient in routine patient care. 2 To perform EEG-based monitoring of delirium with a limited number of electrodes, we studied the optimal electrode derivation and EEG characteristic to discriminate delirium from non-delirium. Methods: Standard EEGs were recorded in 28 delirious and 28 age- and gender-matched non-delirious postoperative cardiac surgery patients. A geriatrician, psychiatrist or neurologist evaluated the patient for delirium using the Diagnostic and Statistical Manual of mental disorders IV criteria. The first minute of artefact-free data with eyes closed and with eyes open was selected. For eyes-closed recordings, all possible bipolar derivations were studied, while for eyes-open only occipital and parietal electrodes were used. For each derivation, 6 EEG parameters were evaluated: relative power in the delta, theta, alpha and beta frequency band, peak frequency and slow-fast ratio. Using a Mann-Whitney U-test, all combinations of derivations and parameters were compared between delirious and non-delirious patients and p-values were ranked and corrected for multiple testing (eyes closed alpha adjusted =4.0*10-5 ; eyes openalpha adjusted =5.6*10-4 ). Results: There were no significant differences between patients with and without delirium in age (mean ± SD 76 ± 5.7 versus 74 ± 8.6; p=0.21), gender (n=14 (54%) males versus n=16 (57%) males; p=0.81), bypass time (median (interquartile range) 129 (95-158) versus 108 (77-168); p=0.07) and Euroscore (median (interquartile range) 7 (6-9) versus 7 (5-8); p=0.17). Table 1 lists the 10combinations of EEG derivations and EEG characteristics with the lowest p-value for the eyes closed condition, while table 2 lists these 10 combinations for the eyes open condition. When comparing the eyes-closed with eyes-open condition, the p-value for the best derivation and characteristic for eyes-closed was smaller than for eyes-open. With eyes closed, the optimal combination of electrode derivation and EEG characteristic was F8-Pz and relative delta power (p=1.8*10-12, table 1). Also neighboring electrodes of

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